Recording Cell Lineage and History

A fundamental challenge in biology is reconstructing the lineage relationships and molecular event histories through which individual cells grow and differentiate to form multicellular tissues, organisms, and tumors, and understanding how key decision points are controlled. Despite powerful techniques, achieving this goal remains difficult in most contexts. To address this, we are developing MEMOIR, a synthetic genetic system that allows cells to actively record information at engineered memory elements within their genome in a format that can be read out by single-molecule FISH imaging. I will discuss efforts to engineer MEMOIR recording systems. In addition, I will also discuss recent work suggesting that lineage specification events can ultimately be determined by stochastic activation events at single genetic loci.